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Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT) (COBRIT)

Primary Purpose

Traumatic Brain Injury

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Placebo
citicoline
Sponsored by
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring traumatic brain injury, cognition, behavioral outcome, functional outcome, treatment, early intervention, citicoline

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Non-penetrating traumatic brain injury.
  2. Age 18 (19 in Alabama) - 70 years.
  3. GCS criteria on/off paralytics as specified in protocol
  4. Reasonable expectation of completion of outcomes measures at a network center at six months post-injury.
  5. Able to swallow oral medication or, if unable to swallow, a gastric tube or peg are placed by 23 hours after injury.
  6. Reasonable expectation of enrollment within 24-hour time window.
  7. English-speaking

Exclusion Criteria:

  1. Intubated patients with GCS motor score = 6 and not meeting CT criteria.
  2. Bilaterally fixed and dilated pupils
  3. Positive pregnancy test, known pregnancy, or currently breast feeding
  4. Evidence of diseases that interfere with outcome assessment
  5. Current acetylcholinesterase inhibitor use (Appendix 1)
  6. Imminent death or current life-threatening disease
  7. Currently enrolled in another study
  8. Prisoners

Sites / Locations

  • University of Alabama at Birmingham
  • University of Maryland, Baltimore
  • Temple University
  • University of Pittsburgh
  • University of Tennessee Health Sciences Center
  • University of Texas, Southwestern Medical Center
  • Virginia Commonwealth University
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Placebo

Citicoline

Arm Description

Placebo tablets formulated to resemble the citicoline treatment.

Experimental treatment administered orally or enterally depending upon whether the participant can swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.

Outcomes

Primary Outcome Measures

Functional and Cognitive Outcome
The primary outcome of this study was analyzed using a global statistic of the Network Core Battery. There were 9 scales: California Verbal Learning Test II (CVLT-II); Controlled Oral Word Association Test (COWAT); Digit Span (DS); Glasgow Outcome Scale Extended (GOSE); Processing Speed Index (PSI); Stroop Test 1 and 2 (ST1&2); and Trail Making Test part A and B (TMT parts A and B). Each scale was assigned cut-off for good outcome: GOSE>7, CVLT>36, PSI>85, TMT part A <42, TMT part B<138.1, DS>7.15, ST1<60.29, ST2<151.47, COWAT>32.5. Logistic regression was used to estimate the global OR.

Secondary Outcome Measures

Full Information

First Posted
October 16, 2007
Last Updated
November 16, 2012
Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT00545662
Brief Title
Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT)
Acronym
COBRIT
Official Title
Citicoline Brain Injury Treatment Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2012
Overall Recruitment Status
Terminated
Why Stopped
Trial stopped due to futility.
Study Start Date
July 2007 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The Citicoline Brain Injury Treatment (COBRIT) is a randomized, double-blind, placebo controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate and severe traumatic brain injury.
Detailed Description
Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established in either the acute or post acute setting. Citicoline is a naturally occurring endogenous compound. This compound offers the potential of employing neuroprotection, neuro-recovery and neurofacilitation to enhance recovery after TBI. The primary goal of this study is to assess the efficacy of citicoline compared to placebo on functional and cognitive outcome in participants with traumatic brain injury.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury
Keywords
traumatic brain injury, cognition, behavioral outcome, functional outcome, treatment, early intervention, citicoline

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1213 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Experimental
Arm Description
Placebo tablets formulated to resemble the citicoline treatment.
Arm Title
Citicoline
Arm Type
Experimental
Arm Description
Experimental treatment administered orally or enterally depending upon whether the participant can swallow at 1,000 mg twice a day for 90 days or until the 90-day outcome assessment.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Drug Placebo Inactive twice a day given orally or enterally. The first dose is given within 24 hours of injury and treatment continues until 90 days or until the 90-day outcome assessment.
Intervention Type
Drug
Intervention Name(s)
citicoline
Other Intervention Name(s)
CDP-Choline, Cytidine 5-diphosphocholine, Somazina
Intervention Description
1000 mg twice a day orally or enterally. The first dose is within 24 hours of injury and treatment continues for 90-days or until the 90-day outcome assessment.
Primary Outcome Measure Information:
Title
Functional and Cognitive Outcome
Description
The primary outcome of this study was analyzed using a global statistic of the Network Core Battery. There were 9 scales: California Verbal Learning Test II (CVLT-II); Controlled Oral Word Association Test (COWAT); Digit Span (DS); Glasgow Outcome Scale Extended (GOSE); Processing Speed Index (PSI); Stroop Test 1 and 2 (ST1&2); and Trail Making Test part A and B (TMT parts A and B). Each scale was assigned cut-off for good outcome: GOSE>7, CVLT>36, PSI>85, TMT part A <42, TMT part B<138.1, DS>7.15, ST1<60.29, ST2<151.47, COWAT>32.5. Logistic regression was used to estimate the global OR.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Non-penetrating traumatic brain injury. Age 18 (19 in Alabama) - 70 years. GCS criteria on/off paralytics as specified in protocol Reasonable expectation of completion of outcomes measures at a network center at six months post-injury. Able to swallow oral medication or, if unable to swallow, a gastric tube or peg are placed by 23 hours after injury. Reasonable expectation of enrollment within 24-hour time window. English-speaking Exclusion Criteria: Intubated patients with GCS motor score = 6 and not meeting CT criteria. Bilaterally fixed and dilated pupils Positive pregnancy test, known pregnancy, or currently breast feeding Evidence of diseases that interfere with outcome assessment Current acetylcholinesterase inhibitor use (Appendix 1) Imminent death or current life-threatening disease Currently enrolled in another study Prisoners
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sherry Melton, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Howard Eisenberg, MD
Organizational Affiliation
University of Maryland, Baltimore
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jack Jallo, MD, PhD
Organizational Affiliation
Temple University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joseph Ricker, PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shelly Timmons, MD, PhD
Organizational Affiliation
University of Tennessee Health Sciences Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ramon Diaz-Arrastia, MD, PhD
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Ward, MD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nancy Temkin, PhD
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Beth Ansel, PhD
Organizational Affiliation
National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
William Friedewald, MD
Organizational Affiliation
Columbia University Department of Biostatistics
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3295
Country
United States
Facility Name
University of Maryland, Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Temple University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141-3099
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-3221
Country
United States
Facility Name
University of Tennessee Health Sciences Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
University of Texas, Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0677
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
23298-0631
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23168823
Citation
Zafonte RD, Bagiella E, Ansel BM, Novack TA, Friedewald WT, Hesdorffer DC, Timmons SD, Jallo J, Eisenberg H, Hart T, Ricker JH, Diaz-Arrastia R, Merchant RE, Temkin NR, Melton S, Dikmen SS. Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA. 2012 Nov 21;308(19):1993-2000. doi: 10.1001/jama.2012.13256.
Results Reference
derived

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Study of Citicoline for the Treatment of Traumatic Brain Injury (COBRIT)

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